Abstract: Interleukin 6 (IL-6) is a typical pleiotropic cytokine that modulates a variety of physiological events in vertebrates, including cell proliferation, differentiation, survival, and apoptosis, among other functions. IL-6 plays roles in the immune, the endocrine, the nervous, and the hematopoietic systems, in bone metabolism, regulation of blood pressure and inflammation. IL-6 exerts its effects on different tissues and organ systems. Many cell types are reported to produce IL-6: T cells, B cells, polymorphonuclear cells, eosinophils, monocyte/macrophages, mast cells, dendritic cells, chondrocytes, osteoblasts, endothelial cells, skeletal and smooth muscle cells, islet cells, thyroid cells, fibroblasts, mesangial cells, keratinocytes, microglial cells, astrocytes, oligodendrocytes, adipose tissue and certain tumor cells. In this article we review the participation of the IL-6 in the neuroimmunoendocrine network that includes all interactions across species, sexes, cells, and types of responses. Additionally, we discuss the information that is available so far about the production of IL-6 by the neural cell populations, the role that this cytokine plays at the local level in the modulation of some physiological neural actions, as well as its participation in the development and progression of neuroinflammation and the neurodegenerative process. Considering the multiple functions that IL-6 plays as an endocrine and neural regulator, the specific targeting of the IL-6 pathway can be a promising new approach for the treatment and prevention of neurodegenerative disorders in humans. Furthermore, blocking the effect of IL-6 may improve the autoinflammatory process both systemically and locally.